Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction.

Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis.

The angiotensin receptor neprilysin inhibitor LCZ696 attenuates renal fibrosis via ASK1/JNK/p38 MAPK-mediated apoptosis in unilateral ureteral obstruction.

The angiotensin receptor neprilysin inhibitor LCZ696 affords superior cardioprotection and renoprotection compared with renin-angiotensin blockade monotherapy, but the underlying mechanisms remain elusive. Herein, we evaluated whether LCZ696 attenuates renal fibrosis by inhibiting ASK1/JNK/p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Rats with UUO were treated daily for 7 days with LCZ696, valsartan, or the selective ATP competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1), GS-444217.

Inhibition of RIP1-RIP3-mediated necroptosis attenuates renal fibrosis via Wnt3α/β-catenin/GSK-3β signaling in unilateral ureteral obstruction.

Renal fibrosis represents the final common outcome of chronic kidney disease of virtually any etiology. However, the mechanism underlying the evolution of renal fibrosis remains to be addressed. This study sought to clarify whether RIP1-RIP3-mediated necroptosis is involved in renal fibrosis via Wnt3α/β-catenin/GSK-3β signaling in vitro and in a rat model of unilateral ureteral obstruction (UUO).

Coenzyme Q10 attenuates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in unilateral ureteral obstruction.

Objective: Coenzyme Q10 (CoQ10) protects against various types of injury, but its role in preventing renal scarring in chronic kidney disease remains an open question. Herein, we evaluated whether CoQ10 attenuates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro.

Methods: Rats with UUO were treated daily with CoQ10 or an RIP inhibitor (necrostatin-1 or GSK872) for 7 days.

Dapagliflozin Alleviates Renal Fibrosis by Inhibiting RIP1-RIP3-MLKL-Mediated Necroinflammation in Unilateral Ureteral Obstruction.

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, offers renoprotection in diabetes. However, potential for use in nondiabetic kidney disease remains unknown. Herein, we assessed whether dapagliflozin alleviates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and .

Exogenous pancreatic kininogenase protects against tacrolimus-induced renal injury by inhibiting PI3K/AKT signaling: The role of bradykinin receptors.

Background: Tissue kallikrein offers a wide spectrum of biological activity in the protection against various types of injury. However, information on its role in tacrolimus (TAC)-induced renal injury is limited.

Objectives: This study aimed to assess the beneficial effects of pancreatic kininogenase (PK) in a rat model of chronic TAC nephrotoxicity and in vitro.

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death.

Background/aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction.

Background/aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro.

L-Carnitine protects against tacrolimus-induced renal injury by attenuating programmed cell death via PI3K/AKT/PTEN signaling.

Reducing immunosuppressant-related complications using conventional drugs is an efficient therapeutic strategy. L-carnitine (LC) has been shown to protect against various types of renal injury. In this study, we investigated the renoprotective effects of LC in a rat model of chronic tacrolimus (TAC) nephropathy.

Exogenous pancreatic kininogenase protects against renal fibrosis in rat model of unilateral ureteral obstruction.

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and HO-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7.

Expression of brain-derived neurotrophic factor in kidneys from normal and cyclosporine-treated rats.

Background: Accumulating evidence suggests that a decrease in brain-derived neurotrophic factor (BDNF) level induces a variety of psychiatric and neurological disorders. However, the expression and role of BDNF in the kidney have not been explored. The present study examined the expression of BDNF and tropomyosin-related kinase (Trk) receptors in an experimental model of chronic cyclosporine A (CsA) nephropathy.

Shen-Kang protects against tacrolimus-induced renal injury.

Background/aims: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy.

Methods: Rats were treated daily with TAC (1.

Dipeptidyl peptidase IV inhibitor MK-0626 attenuates pancreatic islet injury in tacrolimus-induced diabetic rats.

Background: Tacrolimus (TAC)-induced pancreatic islet injury is one of the important causes of new-onset diabetes in transplant recipients. This study was performed to evaluate whether a dipeptidyl peptidase IV (DPP IV) inhibitor is effective in improving TAC-induced diabetes mellitus by reducing pancreatic islet injury.

Methods: Rats were treated with TAC (1.

Synergistic effects of leflunomide and benazepril in streptozotocin-induced diabetic nephropathy.

Background: Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies.

Methods: Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats.

Combined treatment of tacrolimus and everolimus increases oxidative stress by pharmacological interactions.

Background: Drug-drug interaction between everolimus (EVR) and tacrolimus (TAC) is still undetermined. We evaluated whether EVR enhances TAC-induced organ injury through drug-drug interaction.

Methods: Tacrolimus (6 mg/kg) was given to rats with or without EVR (1 or 2 mg/kg) orally for 4 weeks.

Ginseng treatment attenuates autophagic cell death in chronic cyclosporine nephropathy.

Aims: Chronic cyclosporine (CsA) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy.

Methods: Mice were treated with CsA (30 mg/kg) with or without Korean red ginseng (KRG) extract (0.

Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

Background: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury.

Methods: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.

Influence of N-acetylcysteine on Klotho expression and its signaling pathway in experimental model of chronic cyclosporine nephropathy in mice.

Background: Cyclosporine A (CsA)-associated oxidative stress has been proposed as an important mechanism of renal injury. This study was designed to examine whether N-acetylcysteine (NAC), a well-known antioxidant, affects Klotho, antiaging gene, expression and its signaling pathway in an experimental model of chronic CsA nephropathy.

Methods: Mice maintained on a low-sodium diet were given vehicle (olive oil, 1 mL/kg/day), CsA (30 mg/kg/day), NAC (150 mg/kg/day), or a combination of CsA and NAC for 4 weeks.

Ginseng treatment attenuates chronic cyclosporine nephropathy via reducing oxidative stress in an experimental mouse model.

Background: This study was performed to investigate whether ginseng extract has a protective effect in an experimental mouse model of chronic cyclosporine (CsA) nephropathy.

Methods: Mice were treated with CsA (30 mg/kg/day, subcutaneously) with or without Korean red ginseng extract (KRG) (0.2, 0.

Human adipose tissue derived mesenchymal stem cells aggravate chronic cyclosporin nephrotoxicity by the induction of oxidative stress.

The aim of this study was to investigate whether hATMSCs protect against cyclosporine (CsA)-induced renal injury. CsA (7.5 mg/kg) and hATMSCs (3×10(6)/5 mL) were administered alone and together to rats for 4 weeks.

Statin upregulates the expression of klotho, an anti-aging gene, in experimental cyclosporine nephropathy.

Background: We recently reported that long-term cyclosporine (CsA)-induced oxidative stress is associated with decreased expression of klotho, an anti-aging gene. This study evaluated whether the antioxidant effect of statin might upregulate klotho expression in CsA-induced renal injury.

Methods: Two separate experiments were performed.

Dysregulation of Th17 cells during the early post-transplant period in patients under calcineurin inhibitor based immunosuppression.

Accumulating evidence suggests that Th17 cells play a role in the development of chronic allograft injury in transplantation of various organs. However, the influence of current immunosuppressants on Th17-associated immune responses has not been fully investigated. We prospectively investigated the changes in Th17 cells in peripheral blood mononuclear cells (PBMCs) collected before and 1 and 3 months after KT in 26 patients and we investigated the suppressive effect of tacrolimus on Th17 in vitro.

Determination of rituximab dose according to immunologic risk in ABO-incompatible kidney transplantation.

The adequate rituximab (RTX) dosage in ABO-incompatible transplantation (ABO-IKT) remains undetermined. We used two kinds of RTX dosage groups [low RTX (100 mg/m(2)) and typical RTX (375 mg/m(2)) dosage groups] according to immunologic risks and investigated the change of B-cell, anti-ABO antibodies, and the clinical outcome in ABO-IKT according to the RTX dose. Fifteen patients with high immunologic risk [panel reactive antibody (PRA) > 50%, retransplant, AB to O transplant] were assigned to typical RTX group and 17 patients without risk were assigned to low RTX group.

Chronic cyclosporine nephropathy is characterized by excessive autophagosome formation and decreased autophagic clearance.

Background: The study was performed to investigate the influence of cyclosporine A (CsA)-induced renal injury on autophagy in an experimental model of chronic CsA nephropathy.

Methods: Three dosages of CsA (7.5, 15, and 30 mg/kg/day) were administered to mice for 4 weeks.